Many medicaments take the form of a suspension of particles in a carrier liquid. Typically the size of a medicament particle is less than 10 micrometers. An example of such a particle is a glucocorticosteroid particle.
These suspensions are often sterile and are stored in containers made from polymeric materials having thermoplastic properties that allow them to be easily moulded into appropriate shapes for storage containers.
Typically the storage container is shaped to allow easy dispensing of the medicament from the container by squeezing the container. The dispensing of the medicament is usually achieved by manually squeezing the container so that the container is deformed. The increased pressure in the container forces the liquid out of the container through an opening.
EP1133969 discloses a container for liquid or pasty substances or powders, suspensions or liposomial preparations, for pharmaceuticals, diagnostics, cosmetics or similar, enclosed in a plate of plastic material, comprising two semi-containers with bodies and necks, close together and parallel. Pre-cut lines are provided and at least some of these concern the said necks, in such a way as making a separation along these pre-cut lines causes the selective opening of a semi-container, or of both of them, and therefore the dispensing of a half dose or of the entire dose of the product in the container. A set of containers is also described, comprising a plurality of containers joined between themselves along lines of breakable joints and that allow their separation at the moment of use.
WO2004/039369 relates to a single-use container for a topically applied medicament or cosmetic agent, comprising a single dose of melatonin or melatonin derivative, which corresponds to a locally effective dose but does not have any systemic effect.
EP0743057 discloses a soft gelatin capsule containing a medicament and comprises a flexible hollow shell having a bulb with a tampered section leading to a removal tab integrally formed therewith, the junction between the tab and the tapered section defines an expulsion port. The bulb is in the form of any elongate body having top and bottom flattened portions which portions are provided with knurled texture regions.
GB2079238 disclosed a container made of low-density polyethylene coated on at least one side with a sealant film having an outlet which is closed by a closure tab which can be permanently separated from the remainder of the container along a weakened portion for dispensing one dose of medicament such as 0.5 to 5 g of an anti-inflammatory steroid formulation contained therein. A plurality of such containers can be connected at the tab and/or body to form a strip. The film, which may be derived from cellulose, an acrylic resin, or polyvinyl chloride, is formed by coating with a solution, dispersion or foam of the polymer is a suitable medium after pre-treating the substrate polyethylene by corona discharge, ionizing radiation, or an oxidizing agent. The coating operation is preferably performed after filling and closing the containers.
GB823155 discloses a sterile, single-dose, multiple-unit package of medicament, and a method for making the same.
Frequently the storage container will not be used immediately by the pharmacist, hospital or patient so it is necessary to store the container for an extended period of time. Storage of suspensions in such containers frequently leads to settling of the particles out of the carrier liquid and deposition on the container walls. The suspension may settle in such a way that it is not easily re-suspended by gentle shaking or flicking the container with, for example, a finger.
If the container is stored upright, i.e. the base of the container downwards, the particles will settle at the base of the container and may be easily re-suspended by the user prior to use. However, frequently the container is inadvertently stored in an inverted orientation, i.e. the dispensing portion and orifice is downwards. Consequently the particles settle in the dispensing portion near the orifice. Re-suspension of the sedimented particles is made difficult because of the narrowed cylindrical and/or tapered shape of the dispensing portion that is frequently used by manufacturers. The narrowed cylindrical tapering shape of the dispensing portion acts to restrict the free flow of the medicament in the dispensing portion. The narrowed tapering shape also restricts the ability of the medicament to form a vortex, or other type of turbulent flow, which will dislodge the sedimented particles from the wall, at or near the distal end (orifice end) of the dispensing portion. This may be due to, amongst other factors, a surface tension effect in the dispensing portion near the orifice. Re-suspension may require multiple inversions and repeated flicking of the container in order to detach the particles from the container walls. Agglomeration of the particles into clumps of particles comprising multiple particles is also a problem.
This settling, and subsequent inadequate re-suspension, reduces the effective amount of the medicament that is suspended in the carrier liquid. Consequently the effective dose that a patient will receive when the suspension is dispensed from the container is also reduced. If the size of the particle is crucial to the delivery of the medicament to the affected site in the patient, e.g. inhaled glucocorticosteroids in asthma patient's lungs, then disintegration of clumps of particles is important. If the patient is old, weak, or impatient it is more likely that they will be unable to effectively re-suspend the particles into the suspension or will inadequately re-suspend the particles. In both cases the patient will receive a reduced, or variable, dose of the medicament. Such a dose may be inadequate for the patients needs.